Crohn""s disease persists as an enigma: without a deciphered etiology and without adequate therapy. Prevailing explanations of the pathogenesis of Crohn""s disease (Crohn""s Disease) hold that the characteristic chronic intestinal inflammation results from an aberrant, activated immune response generated against ubiquitous bacteria or bacterial products that gain access to the lamina propria, perhaps through a more permeable intestinal barrier. The abnormal reaction has been suggested to be mediated principally by T-cells enhanced by an intrinsic imbalance in pro-inflammatory and contra-inflammatory mediators. Thus, most therapy aims to counteract that inflammatory state with increasingly potent and sophisticated immune suppressants.
Current therapy, mostly directed at suppressing the inflammatory process, remains inadequate both for the treatment of flares and maintenance of remission. Steroids can be effective in short term use but produce dependency in a significant proportion of patients. While certain antibiotics appear promising, data are limited. Thus there is a need in the art for effective method for treating inflammatory bowel diseases.
It is an object of the invention to provide a method of treating Crohn""s Disease.
It is an object of the invention to provide a method of treating Ulcerative Colitis.
It is another object of the invention to provide a method of treating extrainstestinal manifestations of Ulcerative Colitis or Crohn""s disease.
It is still another object of the invention to provide a method of treating pouchitis.
It is yet another object of the invention to treat and reduce the risk of fistula recurrence.
These and other objects of the invention are provided by one or more of the embodiments described below. In one embodiment a method is provided of treating Crohn""s Disease in which an immune stimulatory amount of an agonist of CD114 (Granulocyte Colony Stimulating Factor Receptor (G-CSFR)) is administered to a patient with Crohn""s Disease not associated with Glycogen Storage Disease 1b.
In another embodiment of the invention another method of treating Crohn""s Disease is provided. An immune stimulatory amount of an agonist of CD 116 (Granulocyte-Macrophage Colony Stimulating Factor Receptor) or CDw131 is administered to a patient with Crohn""s Disease not associated with Glycogen Storage Disease 1b.
In yet another embodiment of the invention another method is provided of treating Crohn""s Disease. An immune stimulatory amount of an agonist of CD114 (Granulocyte Colony Stimulating Factor Receptor (G-CSFR)) is administered to a patient with Crohn""s Disease not associated with Chronic Granulomatous Disease.
In still another embodiment of the invention a method is provided of treating Crohn""s Disease in which an immune stimulatory amount of an agonist of CD116 (Granulocyte-Macrophage Colony Stimulating Factor Receptor) or CDw131 is administered to a patient with Crohn""s Disease not associated with Chronic Granulomatous Disease.
In even another embodiment of the invention another method is provided of treating Crohn""s Disease. An immune stimulatory amount of an agonist of CD114 (Granulocyte Colony Stimulating Factor Receptor (G-CSFR)) is administered to a patient with Crohn""s Disease not associated with a presently characterized and identifiable specific neutrophil disorder caused by a genetic disease.
In yet another embodiment of the invention another method is provided of treating Crohn""s Disease. An immune stimulatory amount of an agonist of CD116 (Granulocyte-Macrophage Colony Stimulating Factor Receptor) or CDw131 is administered to a patient with Crohn""s Disease not associated with a presently characterized and identifiable specific neutrophil disorder caused by a genetic disease.
According to another aspect of the invention a method is provided of treating Ulcerative Colitis. An immune stimulatory amount of an agonist of CD114 (Granulocyte Colony Stimulating Factor Receptor (G-CSFR)) is administered to a patient with Ulcerative Colitis.
According to another aspect of the invention a method is provided of treating Ulcerative Colitis. An immune stimulatory amount of an agonist of CD116 (Granulocyte-Macrophage Colony Stimulating Factor Receptor) or CDw131 is administered to a patient with Ulcerative Colitis.
Another aspect of the invention is a method of treating extraintestinal manifestations of Ulcerative Colitis. An immune stimulatory amount of an agonist of CD114 (Granulocyte Colony Stimulating Factor Receptor (G-CSFR)) is administered to a patient with extraintestinal manifestations of Ulcerative Colitis.
Another aspect of the invention is a method of treating extraintestinal manifestations of Ulcerative Colitis. An immune stimulatory amount of an agonist of CD116 (Granulocyte-Macrophage Colony Stimulating Factor Receptor) or CDw131 is administered to a patient with extraintestinal manifestations of Ulcerative Colitis.
According to still another aspect of the invention a method is provided of treating pouchitis. An immune stimulatory amount of an agonist of CD114 (Granulocyte Colony Stimulating Factor Receptor (G-CSFR)) is administered to a patient with pouchitis.
According to still another aspect of the invention a method is provided of treating pouchitis. An immune stimulatory amount of an agonist of CD116 (Granulocyte-Macrophage Colony Stimulating Factor Receptor) or CDw131 is administered to a patient with pouchitis.
According to still another aspect of the invention a method is provided of preventing or reducing the risk of fistula recurrence. An immune stimulatory amount of an agonist of CD114 (Granulocyte Colony Stimulating Factor Receptor (G-CSFR)) is administered to a patient with Crohn""s disease who has previously had a fistula, whereby the risk of recurrence of a fistula is reduced.
According to still another aspect of the invention a method is provided of preventing or reducing the risk of fistula recurrence. An immune stimulatory amount of an agonist of CD116 (Granulocyte-Macrophage Colony Stimulating Factor Receptor) or CDw131 is administered to a patient with Crohn""s disease who has previously had a fistula, whereby the risk of recurrence of a fistula is reduced.
The present invention thus opens a new realm of treatment modalities for inflammatory bowel diseases which have proven refractory to discovery of safe and effective ministrations. Contrary to the prior paradigm in the art of treating inflammatory bowel diseases with immunosuppressive agents, the present invention uses agents known to be immunostimulatory to treat, prevent, and maintain remission of such diseases.